The Experimental Study About The Relationship Between Wnt/β-catenin Pathway And Abnormal Activation Of Hair Follicle Stem Cells Induced By TPA

Normally, the cycle growth of hair follicle depends on the cycle activation and silence ofhair follicle stem cell. However, hair follicle stem cell can keep being abnormally activatedby some physical and chemical factors, causing hair follicle stem cell exhausted or theproduction of skin neoplasm. Besides Wnt/β-catenin signaling pathway plays a key role inactivating hair follicle stem cell and inducing telogen hair follicle into anagen hair follicle.But what is known little is the role of the signaling pathway in the abnormal activation ofhair follicle stem cell and the relationship between the signaling pathway and the factorinducing the abnormal activation of hair follicle stem cell. TPA, a tumor promoter, canmake the abnormal activation of hair follicle stem cell.TPA has been used to with DMBAdose on the skin to produce neoplasms. In our work, we examined the expression of the keymolecules of Wnt/β-catenin signaling pathway in the skin delt with TPA alone and TPAcombining with DMBA. And after the signaling pathway was blocked, we analysied theactivity of hair follicle stem cell induced by TPA in order to test whether the signalingpathway takes part in the process of the abnormal activation of hair follicle by TPA.Objective, By the analysis of the expression of the key molecules of Wnt/β-cateninsignaling pathway in skin dosed by TPA alone and combining with DMBA, and theabnormal activation of hair follicle stem cell after the signaling pathway is blocked, wewant to study the effect of Wnt/β-catenin signaling pathway in the process of hair folliclestem cell and the relationship between the signaling pathway and the factor inducing theactivation of hair follicle stem cell.Methods,1、Our study used TPA and acetone to dose the back skin of7weeks oldfemale mouse for1、2、4weeks respectively. HE staining was used to show the morphologicchange, immunofluorescence technology used to examine the activity of hair follicle stemcell. And RT-PCR、Western blot and immunofluorescence technology were used to find the change of Wnt/β-catenin signaling. Finally, we performed the intradermal injection ofDKK1and N1plasmid respectively into the skin with treatment of TPA for4weeks andused the HE staining to observe the morphologic change and immunofluorescencetechnology to examine the change of Wnt/β-catenin signaling and activity of hair folliclestem cell.2、Our study further demonstrated the morphologic character of sebaceousneoplasm induced by treatment of DMBA/TPA by HE staining, the immune phenotype ofsebaceous neoplasm, the activity of hair follicle stem cell and change of Wnt/β-cateninsignaling.Results,1、Our work further demonstrated that TPApromoted the telogen hair follicleinto anagen hair follicle by activating the hair follicle stem cell;2、We firstly found thatafter the TPA treatment Wnt/β-catenin signaling was up-regulation in hair folliclekeratinocyte;3、After the Wnt/β-catenin signaling was targetably inhibited in the back skinof mouse dosed with TPA, the growth of some of hair follicles were regressed and in thesehair follicles, the activity of hair follicle stem cells was inhibited.4、On the other hand, ourstudy showed that special markers of hair follicle differentiation expressed in the sebaceousneoplasm;5、And we further found activated hair follicle stem cells existed in thesebaceous neoplasm;6、Wnt/β-catenin signaling was activated in some of sebaceousneoplasm cells.Conclusion,1、Wnt/β-catenin signaling is required for TPA inducing excrescent hairfollicle;2、The key molecules of Wnt/β-catenin signaling and hair follicle stem cell takepart in the development of DMBA/TPA induced sebaceous neoplasm.